The relationship between eosinophils and reduction in major adverse cardiac events in ETHOS

Background: In the Phase III, 52-wk ETHOS trial (NCT02465567) in COPD, budesonide/glycopyrronium/formoterol (BGF) triple therapy significantly reduced all-cause mortality risk (ACM, HR 0.51; unadjusted p=0.0035) vs glycopyrronium/formoterol (GFF) dual therapy. Aim: As cardiovascular (CV) death was the most common cause of ACM and benefits of inhaled corticosteroids (ICS) on COPD outcomes are related to eosinophils (EOS), we performed a post-hoc analysis and examined this for major adverse cardiac events (MACE) in ETHOS. Methods: The effect of BGF 320/14.4/10μg vs GFF 14.4/10µg on fatal and non-fatal MACE and their relationship to EOS was assessed in patients with moderate-to-very severe COPD. Potential MACE were adjudicated by an external committee. Results: Incidence of MACE were numerically lower with ICS-containing therapies (BGF 320: 1.4%; BGF 160: 1.4%; BFF: 1.1%) vs GFF (2.1%). The difference in MACE rates between BGF 320 and GFF on fatal CV events and non-fatal MI was more pronounced as EOS increased (Table). This effect was not seen for non-fatal stroke. Conclusion: Overall, there were fewer MACE in ICS-containing therapy groups than GFF. While event numbers were low, benefits of BGF vs GFF on CV death and non-fatal MI related to higher baseline EOS were consistent with the reduction in ACM with increasing EOS previously observed (Martinez, F.J. et al. Am J Respir Crit Care Med 2020. Epub ahead of print).